IMMUNE BIOMARKERS THAT DIFFERENTIATE ACTIVE TUBERCULOSIS IN CHILDREN

ANA J. BAZAN BOUYRIE; CANDELA MARTÍN; CAMILA MARTINENA; AGUSTIN VITTI; FLORENCIA MOLLEVI,; M. LUZ GARCÍA; SILVINA MARCO, ; RITA ARMITANO; NANCY L. TATEOSIÁN; AMIANO, NICOLÁS O; , GARCÍA V.E

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIAS SAIC・SAFIS ・ ALACF; 2024

The diagnosis of Mycobacterium tuberculosis (Mtb) infection is very challengingin the pediatric population. In children, clinical manifestations of tuberculosis(TB) are often non-specific and disease is usually pauci-bacillary, making it verydifficult to achieve the microbiological diagnosis of active TB. Moreover, bothtuberculin skin test (TST) and IFN-γ release assays (IGRAs) have been shownto have limited usefulness in pediatric cases. Thus, improved tests to diagnoseMtb infection are required. In the present work, we assessed the distinctexpression of immune biomarkers against Mtb specific antigens during activeTB in children. BCG-vaccinated healthy controls (HC) and TB patients between0-14 years old were recruited for this study. Whole blood was stimulated withthe Mtb specific antigen CFP-10-ESAT-6 fusion protein (PF) at 2.5 µg/ml during24 hours. Afterwards, IFN-γ and IP-10 production were tested in plasma byELISA. Furthermore, we used PF at 2.5 µg/ml to sensitize ELISA plates andthen measured IgG specific antibodies in unstimulated plasma samples. Ourresults showed that IFN-γ levels produced against PF allowed to differentiateTB patients from HC (p<0.001, Mann-Whitney test). Accordingly, ROC analysisindicated 100% sensitivity, 100% specificity and a cut-off=66pg/ml. In a similarmanner, the secretion of IP-10 in response to PF showed significantly higherlevels in TB as compared to HC (p<0.01, Mann-Whitney test). Consequently,ROC analysis indicated 100% sensitivity, 100% specificity and a cut-off=123pg/ml. Finally, anti-PF IgG levels allowed to distinguish TB patients fromHC (p<0.05, Mann-Whitney test) with ROC analysis showing 64,71% sensitivityand 95% specificity and a cut-off D.O.=0.32. In summary, our present resultsindicate that the amounts of IFN-γ and IP10 produced against PF together withthe levels of Ig-G anti-PF antibodies might be important tools to identify activeTB in the pediatric BCG-vaccinated population.